Bottlebrush polymers (also referred to a polymer brushes) are macromolecules comprising polymeric sidechains attached to a linear polymeric backbone. Bottlebrush polymers are types of branched or graft polymer, and have unique properties due to their highly branched structure. The high molecular weight and high sidechain grafting density typical of bottlebrush polymers can allow these macromolecules to self-assemble into well-defined structures with large domain sizes. Such properties give these polymers potential applications in, e.g., photonics, chromatography media, stimuli-responsive materials, lubricants, nanolithography, films, coatings, and drug delivery.
Bottlebrush copolymers are bottlebrush polymers comprising two or more different polymeric sidechains (i.e., two or more sidechains of different polymeric composition). These copolymers can be block copolymers, or copolymers wherein the polymeric sidechains are mixed and/or randomly dispersed. For a review on the structure, function, self-assembly, and applications of bottlebrush polymers, see, e.g., Verduzco et al. Chem. Soc. Rev. 2015, 44, 2405-2420, and references cite therein; the entire contents of which are incorporated herein by reference.
Extended release (also referred to as controlled release, sustained release, or time release) technologies allow for the slowed, steadied release of therapeutic agents over an extended period of time. Formulations for extended release of therapeutic agents (e.g., drugs) allow for less frequent dosing or administration, and therefore can increase patient compliance and convenience. Furthermore, implantable materials with extended release characteristics allow for the local administration of therapeutic agents for sustained release to a site of interest. For example, injectable or implantable gels with extended release properties can be administered to the eye of a subject to aid in healing after ocular surgery. As another example, injectable gels can be administered to a tumor site for localized and sustained release of chemotherapeutic agents for the treatment of cancer.
Polymers are useful materials in extended release formulations due to their ability to organize into structures capable of encapsulating, carrying, and/or delivering therapeutic agents. For instance, polymers are known to organize to form particles, micelles, and hydrogels with interesting and attractive drug delivery characteristics, including extended release properties.
Injectable hydrogels based on polymer scaffolds have been reported for non-covalent loading of cargo of various ionic drugs, proteins, and RNAs, and hydrophobic small molecules. Generally, the therapeutic cargo diffuses out of the hydrogel and enters the extracellular matrix; the rate of release is controlled by carrier density and biodegradation. The drug release profiles in vivo from the hydrogels can be tuned by altering the underlying carrier design at molecular level. Of particular interest are polymer systems that are designed to exhibit stimulus-responsive behavior and provide control over the place and duration of drug release. Examples are drug-loaded hydrogels that are modulated or degraded by ECM enzymes, pH, and body heat. In the last group, heat-induced physical crosslinking of drug-loaded micelle solutions is underexplored field and can offer innovative ways of tuning the rate of drug diffusion from carrier hydrogel. New bottlebrush polymers with tunable properties are of great interest. In particular, new bottlebrush polymers capable of forming particles and/or hydrogels have important applications in medicine (e.g., drug delivery).